Be More Agreeable, and Possibly Happier, with TryptophanBy promoting healthy brain serotonin levels, it acts as a kind of “social lubricant”
By Will Block

But if I agreed with you, we’d both be wrong.— Unknown wag

survey by Club Med supposedly showed that couples who were dieting while on their vacation (unclear on the concept!) were about three times as likely to quarrel as those who ate to their hearts’—and stomachs’—content. Conversely, those couples whose hearts and stomachs were happy had about three times as many “romantic interludes” as the dieters. (How did Club Med know? Were they peeking?)

Was there ever a couple who didn’t quarrel from time to time? It’s as natural as . . . making love. The battle of the sexes will never end until men truly understand women, and vice versa—and before that happens, politicians will start deliberately telling the truth. Furthermore, it’s inevitable that individuals of either sex will occasionally lose their cool with someone about something—perhaps a neighbor’s raucous parties, a sales clerk’s insufferable rudeness, or a coworker’s benighted views on illegal immigration.

Whether at home or elsewhere, some ways of engaging the “enemy” are OK, and others just aren’t—they create too much friction. Other than cave dwellers, everyone knows that we should try to be nice to one another. That’s a real challenge, though, for some people—terrorists, for example (oh, wait, they are cave dwellers).

Alas, there are many disagreeable people. Don Rickles made a career of being disagreeable, but he was so funny that he could get away with it. What’s your excuse? Well, not you, of course, just “you” in the generic sense, like, uh, someone you know. (Whew—that was close.) Let’s face it, some people—but not you—could benefit from being more agreeable in their relations with other people. That would surely make both them and the other people happier.

Tryptophan Produces Serotonin, which Regulates Mood

More agreeable . . . happier . . . if only there were a pill one could take. And there is! (It’s a drink-mix powder, actually, but who cares?) It contains tryptophan, a common amino acid that’s found in many foods. Tryptophan is a precursor to serotonin, which is one of our most important neurotransmitters. Serotonin is best known for its key role (along with noradrenaline and dopamine) in the regulation of moods and of emotions such as fear and pleasure. (It’s also, however, involved in learning and memory—see the sidebar.) Deficiencies of this vital compound are known to be associated with aggressive behavior, depression, and even suicide.

Tryptophan May Help Memory Function

Although tryptophan is best known for its antidepressant properties (it’s licensed for use as an antidepressant in a number of countries), it may offer other brain-related benefits as well. There is a growing body of evidence, e.g., that serotonin is involved in the processes of learning and memory and that low serotonin levels impair memory performance in animals and humans.

Researchers at the University of Karachi in Pakistan have studied the effects of long-term tryptophan administration on cognitive performance in rats. In one study, they gave female rats supplemental tryptophan orally for 6 weeks.1 This significantly improved the rats’ performance (compared with the controls) in a maze test of their learning and memory abilities. Postmortem examination of their brains revealed that serotonin metabolism had increased throughout the brain but was most pronounced in the hippocampus, the structure most intimately involved in learning and memory.

In a subsequent study that used a similar protocol, the researchers investigated these processes in more detail.2 They found that tryptophan produced significant improvements in both short-term memory and long-term memory, and they concluded,

Together the neurochemical and behavioral data suggest that increase in serotonergic neurotransmission in the hippocampus plays an important role in improving learning acquisition and memory consolidation in rats. The results further indicate that administration of tryptophan as a dietary supplement may be useful for enhancement of memory functioning.

Serotonin belongs to a class of compounds called monoamines, whose healthy levels in the brain are associated with good mood. Conversely, low levels can spell bad mood. One mechanism by which serotonin levels can decline is via the enzyme monoamine oxidase (MAO). Overactivity of MAO suppresses serotonin levels and can lead to depression. Now you know why drugs called monoamine oxidase inhibitors (MAOIs) are effective antidepressants.

Another way to preserve serotonin is via drugs called selective serotonin reuptake inhibitors (SSRIs), which tend to prevent the reabsorption (reuptake) of serotonin molecules by the neurons that released them, thus making them more available for continued service as neurotransmitters during neural signaling. This makes SSRIs effective antidepressants as well.

The Leaky Can Analogy

But there are other strategies for relieving depression. Rather than use drugs to inhibit the enzyme that reduces serotonin levels or to prevent serotonin reuptake, one can approach serotonin from the upstream side, so to speak—one can boost its synthesis via supplementation with tryptophan so as to offset the losses on the downstream side. Using a leaky can as an analogy, you could plug the leaks with a synthetic goop, or you could pour water into the can fast enough to make up for the leakage.

Recently two studies were published demonstrating some of the benefits of wat . . . uh, tryptophan on our emotional health. Interestingly, they revealed striking differences between the two sexes in terms of the results achieved. It seems that men and women don’t always respond similarly (surprise!) where emotions are involved. In fact, there is considerable evidence that women are more susceptible to manipulation of serotonin levels than men.1

The first study, conducted in Canada, involved 39 exceptionally quarrelsome men and women, average age 32, who were employed, were not alcoholic, and had no major illnesses, including depression.2 How do we know they were so quarrelsome? Because they said so—they were recruited on that very basis, and they provided self-evaluations of their own disagreeable dispositions via questionnaires. The latter invoked terms such as anger, frustration, bitterness, and the “readiness to explode with negative affect at the slightest provocation.” Affect is not a typo—here it’s a psychological term meaning the emotional feeling, tone, or mood attached to a thought, including its external manifestations, such as the behavior it induces.

The researchers sought to determine what effect supplemental tryptophan would have on the subjects’ affect and on four aspects of their behavior—quarrelsome, agreeable, dominant, and submissive—in everyday social interactions with other people (family, coworkers, etc.). Information on how the subjects felt and behaved during each significant conversational interaction (lasting at least 5 minutes) was to be gathered via detailed forms that they would fill out.

Why Use Tryptophan?

The researchers used tryptophan because: (1) it has a relatively specific effect on brain serotonin; (2) it’s a natural dietary component with few side effects and negligible toxicity when given in large amounts; and (3) it has little if any effect on the mood of healthy people (but see the second study, described below, for more on this last factor). Thus, in their opinion, tryptophan was likely to be both effective and safe for disagreeable people, and it was likely to promote agreeableness in such people, but not in people who are pretty nice to begin with.

For 15 days, the subjects took 3 g (3000 mg) of tryptophan or placebo daily, on a blinded basis. There followed a 6-day “washout” period when they took nothing, and then each group took the other agent (placebo or tryptophan) for another 15 days. This represents a “crossover” design, in which each group serves as its own controls. (Unfortunately, the researchers neglected to say how much the subjects griped about the procedure and quarreled with them over how to do it right.*)

*All jokes aside, it’s sobering to note that people who are quarrelsome in everyday social interactions are not only prone to impulsively aggressive behavior in more extreme situations (think road rage, e.g.) but are also at increased risk of hypertension, heart disease, depression, and suicide. Basically, being disagreeable is bad for one’s health.

Men Benefited More than Women from Tryptophan

Overall, the study results showed medium-to-large treatment effects of tryptophan. Affect was improved, i.e., the subjects had more positive and fewer negative emotions—but only when tryptophan was taken during the second half of the study, not the first. All subjects experienced significant declines in quarrelsome behavior (which must have made those around them happy). On the other hand, agreeable behaviors, i.e., those that were distinctly positive and not just “not disagreeable,” increased significantly only in the men, which is odd. Also occurring in the men but not the women were significant decreases in dominant behavior. There were no changes in submissive behavior in either men or women.

Another reported effect was that the men who took tryptophan during the second half of the study perceived the people they interacted with as being more agreeable, in general. No such effect was seen, however, in the men who took it during the first half, or in the women during either half.

The Women Get Even

As if to get even with the men for having benefited disproportionately from tryptophan in the Canadian study, the women participants in the second study mentioned above reaped all the benefits; the men had none.3 This study, conducted in England, sought to assess, in healthy adults, whether tryptophan could induce cognitive changes and emotional biases that are: (1) opposite to those found in clinically depressed individuals, and (2) characteristic of the changes induced by serotonergic antidepressant drugs, i.e., drugs that promote improved serotonin function.

Emotional bias is the tendency to respond either positively or negatively to emotionally charged words or to images that have emotional impact, such as human facial expressions of various kinds (e.g., happiness, sadness, fear, anger, disgust, and surprise). Certain patterns of such biases are characteristic of depression, and their opposites are induced by serotonergic antidepressants—which is, in part, why such drugs work.

In the study, 38 healthy men and women, average age 26, were given 3 g/day of tryptophan or placebo for 14 days. Prior research had indicated that tryptophan has virtually no effect on mood in healthy people, and that was true in this study as well. What tryptophan did do, however, was what the researchers expected: it induced a variety of test responses that were opposite to those seen in depressed individuals and similar to those induced by serotonergic antidepressants.*

*The converse of giving test subjects supplemental tryptophan is giving them a diet (briefly) containing no tryptophan, thereby inducing a transitory state of acute tryptophan depletion, which suppresses serotonin synthesis. It has long been known that this induces a pattern of emotional bias in healthy subjects that’s characteristic of depression, but without altering their mood.

In other words, although it did not literally make the subjects happier, tryptophan provided a kind of biochemical foundation for allowing that to occur, given the right circumstances, namely, a depressed state of mind. In a certain sense, it induced a bias toward a happier state of mind. But it did so only in the women (sorry, guys).

Gettin’ Happy

For as long as the two sexes remain fundamentally different (how about forever, if all goes well?), the battle of the sexes will . . . rage on? Gosh, rage is such an unpleasant concept. Can’t we do better than that? How about boil? Nope—still too hot and messy. Wait—simmer! Yeah, that’s it. Simmer is hot too, but it’s gentle. When Emeril Lagasse has something simmering on the stove, he’s wont to say that the food is “gettin’ happy.”

That’s an agreeable thought, as is the thought that taking tryptophan might just make our lives a little more pleasant, especially when we’re feeling down and could use some happy.